The proposed research will examine (1) effects of chronic neuroleptic administration, and (2) the postsynaptic biochemistry of the dopamine receptor. A number of behavioral, pharmacologic, and biochemical studies in rats will focus on altered receptor senstivity because of its relevance clinically to schizophrenia, tardive dyskinesia, and neuroleptic administration. Studies are designed to identify (1) predispositional factors modifying susceptibility to alteration of receptor sensitivity, (2) biochemical correlates of receptor sensitivity, (3) dopaminergic-cholinergic interaction in states of altered receptor sensitivity, and (4) the potential of dopamine agonists to reverse established receptor supersensitivity. Additional studies will examine the normal ontogenetic development of striatal- and mesolimbic-dopamine-stimulated adenyl cyclase, and the regulation of this enzyme by guanyl nucleotides, ionic alterations, and neurotransmitters. Preliminary work leading to the development of this proposal is presented.